Search Results (18,133)

Background/Objectives: Ascorbic acid (AA)is a micronutrient with concentration-dependent anticancer properties, acting either as a reactive oxygen species (ROS) scavenger or inducer. Methods: Conventional redox-based assays such as MTS/MTT often overestimate cell proliferation due to AA’s interaction with tetrazolium salts, leading to increased formazan production. To overcome this limitation, we employed the Propidium Iodide Triton X-100 (PI/TX-100) assay to evaluate AA’s cytotoxic effects across a diverse panel of cancer and normal cell lines, including prostate (22Rv1, C4-2B, DU-145, LNCaP), breast (MCF-7, MDA-MB-231, MDA-MB-453), lung (A549), liver (HepG2, SK-HEP-1, Huh7), and kidney (Vero) cells. Results: AA significantly suppressed cancer cell viability compared to normal cells (RWPE1 and Vero), with the strongest effects observed in hormone receptor-positive lines. The relative sensitivity to AA followed distinct patterns within each cancer type. Mechanistically, AA-induced cell death involved ROS generation, lipid peroxidation, cell cycle arrest, ferroptosis, apoptosis, and downregulation of pyruvate dehydrogenase kinase 1 (PDHK1). Conclusions: These findings further support the potential of AA as a selective anticancer agent and highlight the importance of assay choice in evaluating its therapeutic efficacy. Full article

Pharmacotherapy in the geriatric population is one of the greatest challenges in modern medicine. Elderly patients, characterized by multimorbidity and the resulting polypharmacy, are significantly more exposed to adverse drug reactions (ADRs), which often lead to hospitalization and a decline in quality of life. Understanding the reasons for this difference requires an analysis of the physiological changes that occur during the aging process at the molecular level. This article presents a perspective on the molecular aspects of geriatric pharmacotherapy, focusing on the fundamental mechanisms that are modified with age. The analysis covers changes in pharmacokinetics, including the role and regulation of cytochrome P450 (CYP) enzymes, whose activity, especially in phase I reactions, is significantly reduced. The age-dependent dysfunction of drug transporters from the ABC (ATP-binding cassette) and SLC (solute carrier) families in key organs such as the intestines, liver and kidneys is discussed, which affects the absorption, distribution and elimination of xenobiotic compounds, including drugs. The article also provides a comprehensive analysis of the blood–brain barrier (BBB), describing changes in neurovascular integrity, including the dysfunction of tight junctions and a decrease in the activity of P-glycoprotein, sometimes referred to as multidrug resistance protein (MDR). This increases the susceptibility of the central nervous system to the penetration and action of drugs. In the realm of pharmacodynamics, changes in the density and sensitivity of key receptors (serotonergic, dopaminergic, adrenergic) are described based on neuroimaging data, explaining the molecular basis for increased sensitivity to certain drug classes, such as anticholinergics. The paper also explores new research perspectives, such as the role of the gut microbiome in modulating pharmacokinetics by influencing gene expression and the importance of pharmacoepigenetics, which dynamically regulates drug response throughout life via changes in DNA methylation and histone modifications. The clinical implications of these molecular changes are also discussed, emphasizing the potential of personalized medicine, including pharmacogenomics, in optimizing therapy and minimizing the risk of adverse reactions. Such an integrated approach, incorporating data from multiple fields (genomics, epigenomics, microbiomics) combined with a comprehensive geriatric assessment, appears to be the future of safe and effective pharmacotherapy in the aging population. Full article

Background and Clinical Significance: Granulomatosis with polyangiitis (GPA), an immune-mediated systemic small-vessel vasculitis affecting the upper/lower respiratory tracts and kidneys, frequently presents with non-specific nasal symptoms that lead to misdiagnosis. Case Presentation: We report a case of a 55-year-old female with GPA complicated by Bartter syndrome. She presented with one month of left nasal congestion, rhinorrhea, epistaxis, and headache. Initial diagnosis was acute sinusitis. Computed tomography (CT) revealed left maxillary and ethmoid sinus inflammation with bone destruction, while metagenomic next-generation sequencing (mNGS) suggested conventional bacterial infection. Postoperative pathology demonstrated chronic mucosal inflammation with lymphoid tissue hyperplasia. GPA was ultimately diagnosed based on PR3-ANCA seropositivity and chest CT findings of cavitary pulmonary nodules. Postoperatively, severe hypokalemia and hypomagnesemia secondary to Bartter syndrome emerged. Following electrolyte correction, induction therapy with glucocorticoids and cyclophosphamide was initiated. Conclusions: This case underscores that GPA’s head and neck manifestations are frequently misdiagnosed as infections or malignancies. Early diagnosis requires vigilance for GPA ‘red flags’, such as refractory nasal symptoms to conventional therapy (e.g., bloody rhinorrhea), characteristic CT findings (e.g., sinus opacification without ostiomeatal complex obstruction), and nasal endoscopy findings (e.g., ulcers/crusting). Otolaryngologists play a pivotal role in recognizing early disease onset and initiating timely treatment. Full article

Although acute kidney injury (AKI) is common among patients with coronavirus disease 2019 (COVID-19), there are only limited data on its occurrence at intensive care unit (ICU) admission. Assessing the factors associated with AKI is essential for early diagnosis and intervention. This study aims to compare the clinical and laboratory characteristics and survival outcomes of COVİD-19 patients with and without AKI at ICU admission and determine the factors associated with AKI. In this study, patients with SARS-CoV-2 infection were categorized based on the presence (AKI group) or absence (non-AKI group) of AKI. Clinical and laboratory data and outcomes were analyzed retrospectively. Of the 712 patients included in this study, 198 were assigned to the AKI group and 514 were assigned to the non-AKI group. Patients with AKI had more comorbidities and higher disease severity; higher rates of invasive mechanical ventilation, vasopressor therapy, and mortality; and longer hospital stays (p < 0.05). Our multivariate analysis identified advanced age, a high Acute Physiology and Chronic Health Evaluation II score, a high neutrophil-to-lymphocyte ratio, a low albumin level, and the presence of comorbidities as independent factors associated with AKI. In patients with COVID-19, AKI observed at ICU admission is associated with advanced age and increased disease severity. The early diagnosis and monitoring of patients may improve clinical outcomes. Full article

Background and Clinical Significance: Cystinuria is the most common genetic cause of pediatric nephrolithiasis, characterized by impaired renal cystine reabsorption and resulting in increased urinary cystine excretion. Due to the poor solubility of cystine at normal urine pH, increased urinary cystine excretion leads to urine supersaturation and precipitation of cystine, resulting in nephrolithiasis. Case Presentation: Here, we report two cases of female patients diagnosed with cystinuria caused by SLC7A9 mutations. Both patients were initially managed with conservative treatments to minimize stone recurrence including increased oral fluid intake, a low-salt/low-protein diet, and potassium citrate supplementation with the goal of reducing urinary cystine levels and minimizing stone recurrences. Due to persistent stone formation, the patients were started on two distinct cystine-binding thiol medications. One patient was initiated on tiopronin, and the other on D-penicillamine. Tiopronin and D-penicillamine are both used in the treatment of pediatric cystinuria, although tiopronin is often preferred due to its more favorable side effect profile. However, due to insurance constraints, D-penicillamine was initiated for one patient in place of tiopronin. Since the initiation of these two distinct cystine-binding thiol medications, both patients have demonstrated reduced urinary cystine excretion and minimal to no recurrence of kidney stones. Conclusions: Cystine-binding thiols, including tiopronin and D-penicillamine, can both be used in the management of cystinuria in pediatric patients. Full article

End-stage chronic kidney disease remains a global challenge, with dialysis and transplantation offering only partial or limited solutions. Recent advances in bioengineering have introduced modular strategies that aim to restore kidney function not by replicating the entire organ, but by rebuilding it one segment at a time. Platforms such as kidney organoids, implantable bioartificial kidneys, 3D-bioprinted tissues, and decellularized scaffolds each target specific nephron functions, from filtration to endocrine signaling. This Perspective examines how these technologies can be integrated into interoperable systems that reflect the nephron’s native structure and functional complexity. We assess translational readiness across key benchmarks, including vascular integration, hormonal responsiveness, immune compatibility, and implantability, and discuss the ethical, regulatory, and design considerations that will shape their clinical future. Collectively, these modular strategies offer a pathway toward more personalized, scalable, and physiologically relevant approaches to kidney replacement. Full article

Background: Trace elements and heavy metals can provide valuable forensic information for individual identification, lifestyle reconstruction, and association with the scene or time of death and may also assist in linking objects to criminal activities. However, the lack of standardized guidelines and post-mortem reference values represents a significant limitation in forensic investigations. Methods: This review was conducted in accordance with the PRISMA statement. We performed a comprehensive literature study over the last ten years focusing on the analysis of trace elements and heavy metals in post-mortem tissues. Results: The search results from the databases yielded 247 records. The screening, according to PRISMA criteria, allowed us to select and include 19 articles. The results showed the need for standardized guidelines and reference values. Although post-mortem trace element analysis shows high potential for forensic applications, substantial methodological heterogeneity persists. Some studies have proposed preliminary reference values for cadmium (Cd) in kidneys and mercury (Hg) in hair but validated post-mortem reference ranges remain largely unavailable. Conclusions: The current literature demonstrates the forensic potential of trace element and heavy metals analysis including Cd, Hg, lead (Pb), Manganese (Mn), Aluminum (Al), Copper (Cu), Zinc (Zn), Iron (Fe), Thallium (Tl), Polonium (²¹⁰Po) but also underlines the urgent need for standardized protocols and validated post-mortem reference values to improve interpretability and reliability in forensic contexts. Full article

Ultrasonic wave attenuation in biological tissues arises from complex interactions between mechanical, structural, and fluidic properties, making it essential to identify dominant mechanisms for accurate simulation and device design. This work introduces a novel integration of experimentally measured tissue parameters into time-explicit nonlinear acoustic wave simulations, in which the equations are directly solved in the time domain using an explicit solver. This approach captures the full transient waveform without relying on frequency-domain simplifications, offering a more realistic representation of ultrasound propagation in heterogeneous media. The study estimates both sound diffusivity and viscous damping parameters (dynamic and bulk viscosity) for a broad range of ex vivo tissues (skin, adipose tissue, skeletal muscle, trabecular/cortical bone, liver, myocardium, kidney, tendon, ligament, cartilage, and gray/white brain matter). Four regression models (power law, linear, exponential, logarithmic) were applied to characterize their frequency dependence between 0.5 and 5 MHz. Results show that attenuation is more strongly driven by bulk viscosity than dynamic viscosity, particularly in fluid-rich tissues such as liver and myocardium, where compressional damping dominates. The power-law model consistently provided the best fit for all attenuation metrics, revealing a scale-invariant frequency relationship. Tissues such as cartilage and brain showed weaker viscous responses, suggesting the need for alternative modeling approaches. These findings not only advance fundamental understanding of attenuation mechanisms but also provide validated parameters and modeling strategies to improve predictive accuracy in therapeutic ultrasound planning and the design of non-invasive, tissue-specific acoustic devices. Full article

Background/Objectives: We sought to evaluate the clinical predictors of underlying histologic activity in patients with lupus nephritis (LN), with a focus on urinary soluble protein CD163 (usCD163). Methods: We conducted a retrospective, cross-sectional study of forty-two consecutive LN patients with concurrent determination of usCD163 at the moment of kidney biopsy. A first morning void prior to the kidney biopsy was collected and usCD163 was measured by a commercial ELISA assay (EUROIMMUN, Lubeck, DE). Results: The study cohort had a median age at the moment of kidney biopsy of 33.5 (IQR: 24–42.7) years. The mean eGFR and median 24 h proteinuria were 76.6 ± 33.9 mL/min/1.73 m² and 1.98 (IQR: 0.83–4.52) g/day. The median activity (AI) and chronicity (CI) indices were 7 (IQR: 3–11) and 3 (IQR: 1–5), respectively. usCD163 significantly correlated with 24 h proteinuria (r = 0.7, p < 0.001), hematuria (r = 0.51, p < 0.001), and serum complement levels, C3 (r = −0.5, p = 0.001) and C4 (r = −0.32, p = 0.03), but not with eGFR (r = −0.23, p = 0.14). Regarding the histological parameters, usCD163 significantly correlated with the AI and the individual active lesions (except for fibrinoid necrosis), but not with CI or any chronic lesion. usCD163 had a higher AUC compared to the classical measures of renal involvement (proteinuria, hematuria, eGFR) for discriminating an elevated AI, but the differences between AUC reached statistical significance only for hematuria. Thus, the AUC of usCD163 was 0.74 (95%CI, 0.58–0.86) for an AI over 2, an AUC of 0.77 (95%CI, 0.61–0.88) for an AI over 3 and an AUC of 0.74 (95%CI, 0.57–0.86) for an AI of at least 9. The optimal cutoff value for usCD163 identified for all AI thresholds evaluated was 296.2 ng/mmol. Conclusions: usCD163 correlates with glomerular inflammation, being able to discriminate histologic activity from chronicity in patients with LN and identify minimal histologic activity, although it did not significantly outperform proteinuria. Full article

Background/Objectives: Systemic toxicities to key organs like the heart, liver, and kidneys impair the efficacy of chemotherapy in cancer treatment. These toxicities are caused by oxidative stress, inflammation, mitochondrial malfunction and ferroptosis, causing clinical morbidity and possibly impaired adherence to treatment. This review, also, examines how magnesium, selenium, zinc and vitamin D protect against chemotherapy-induced cardiotoxicity, hepatotoxicity and nephrotoxicity. Methodology: A complete literature search of PubMed (MEDLINE), Scopus, Cochrane Library and Embase was used to synthesize data till 29 June 2025. Studies included randomized and non-randomized trials, cohort studies, case series (≥3 patients), and relevant systematic reviews. To contextualize pathways, preclinical in vivo and in vitro studies were studied independently. Patients undergoing systemic chemotherapy and magnesium, selenium, zinc or vitamin D therapies were eligible. Supplementation’s safety and organ-specific toxicity were investigated. Results: Magnesium protected against cisplatin-induced nephrotoxicity via modulating renal transporters and oxidative defenses across chemotherapy regimens. Selenium supplementation has strong antioxidant and anti-inflammatory characteristics, especially in avoiding cardiac and hepatic injury, although its nephroprotective potential was formulation-dependent. Zinc’s activity was connected to metallothionein-mediated redox stabilization, inflammatory regulation, and cardiac and hepatic resilience. Vitamin D and its analogs reduced cardiotoxicity and nephrotoxicity through mitochondrial preservation and immunomodulatory signaling. Conclusions: To date, magnesium, selenium, zinc, and vitamin D have been shown to reduce chemotherapy-related organ toxicities. Preclinical studies are promising, but randomized clinical trials are needed to prove therapeutic effectiveness and oncologic safety. Full article

Background and Objectives: The prognostic significance of dynamic changes in glomerular filtration rate (GFR) during targeted therapies in metastatic renal cell carcinoma (mRCC) is not well understood. Thus, we aimed to investigate the prognostic significance of GFR value at 6 months in patients with mRCC receiving first-line targeted therapy. Materials and Methods: This retrospective cohort study included 260 mRCC patients at two tertiary centers in Turkey between 2015 and 2025. Patients were stratified into three groups according to GFR at 6 months: ≥60, 30–60, and <30 mL/min/1.73 m². Kaplan–Meier curves were used to estimate progression-free survival (PFS) and overall survival (OS) in prognostic subgroups. Cox proportional hazard models assessed associations between clinicopathologic variables, including GFR categories, and PFS and OS. Results: The median PFS for the cohort was 11.1 months (95% confidence interval [CI]: 9.3–12.9), and the median OS was 40.0 months (95% CI: 30.3–49.7). In multivariate analysis, GFR < 30 mL/min/1.73 m² was independently associated with shorter PFS (hazard ratio [HR]: 1.54, 95% CI: 1.01–2.33, p = 0.040) and OS (HR: 3.80, 95% CI: 2.06–7.01, p < 0.001), while GFR 30–60 mL/min/1.73 m² was linked to reduced OS (HR: 2.07, 95% CI: 1.08–3.98, p = 0.028). Additional independent predictors of worsened PFS were intermediate (p = 0.028) and poor IMDC risk (p < 0.001. For OS, liver metastases (p = 0.017), bone metastases (p = 0.014), brain metastases (p = 0.002), and intermediate (p = 0.014) or poor IMDC risk (p < 0.001) were also significant. Conclusions: In patients with mRCC treated with targeted therapy, the GFR at 6 months is an independent factor in predicting survival outcomes, indicating the clinical significance of serial kidney function monitoring. Full article

Background and Objectives: Chronic lung diseases act as multi-organ conditions in which systemic inflammation, vascular dysfunction, and fibrosis intersect. The pulmo-renal continuum—functional crosstalk between lungs and kidneys—remains poorly characterized. We compared year-long changes in endothelin-1 (ET-1), galectin-3 (Gal-3), renal indices (eGFR, ACR), and quantitative CT densitometry in COPD and systemic sclerosis-associated ILD (SSc-ILD). Materials and Methods: In this prospective observational study (January 2023–December 2024), 112 patients were consecutively enrolled (COPD, n = 58; SSc-ILD, n = 54). Assessments were performed at baseline and 12 months. ET-1 (ELISA) and Gal-3 (chemiluminescence) were measured in serum; eGFR was calculated by the creatinine-based CKD-EPI (2021) equation; ACR was photometric. High-resolution chest CT provided lung volume and parenchymal density (Hounsfield units) at six predefined axial levels per lung. Non-parametric statistics were applied: Wilcoxon signed-rank (within-group), Mann–Whitney U (between-group), and Spearman rank correlations for associations; results are reported with p-values (and 95% CIs). Results: Baseline eGFR was normal (COPD 90.37; SSc-ILD 92.4 mL/min/1.73 m²). eGFR declined by 6.76% in COPD (p = 0.001) and 3.16% in SSc-ILD (p = 0.029). ET-1 increased in both cohorts but more in COPD (+83.78%, p = 0.0002) than in SSc-ILD (+23.83%, p = 0.0001). Gal-3 rose significantly only in SSc-ILD (+10.2%, p = 0.043). FVC decreased in COPD (−4.01%, p = 0.01) and was unchanged in SSc-ILD. Total lung volume declined in SSc-ILD (−6.08%, p = 0.02) but not in COPD. CT density shifts were small: several slices in COPD and one slice (L6) in SSc-ILD reached statistical but not biological relevance. Conclusions: COPD exhibited larger vascular and renal biomarker shifts (ET-1 up, eGFR down, ACR up), suggesting systemic inflammation and early renal involvement. In SSc-ILD, biomarker and CT changes predominantly reflected pulmonary fibrosis progression with limited renal impact. Integrating biomarkers with quantitative CT may help delineate organ-specific trajectories along the pulmo-renal continuum; longer, larger studies are warranted. Limitations: This was a single-center cohort with a modest sample (58 COPD and 54 SSc-ILD) and a 12-month, two-time-point follow-up, which may not capture long-term trajectories and may limit it generalizability; larger multicenter studies with an extended follow-up are warranted. Full article

Acute inflammation is frequently triggered by pathogen infections and contributes to host mortality. In this study, a new exopolysaccharide (ObEPS) was isolated from the moss endophyte Ovatospora brasiliensis and characterized for its structure and biological activity. Monosaccharide composition analysis revealed that ObEPS was mainly composed of galactose, glucose, mannose, and glucuronic acid. Multi-angle light scattering and conformation analysis showed a molar mass of 10⁵–10⁶ Da and a compact chain conformation. In vitro experiments showed that ObEPS markedly inhibited nitric oxide production and reduced pro-inflammatory cytokine expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. In a systemic Candida albicans infection model, ObEPS combined with fluconazole significantly reduced fungal colony-forming units (CFUs)/g kidney from 3.8 × 10⁵ to 0.1 × 10⁵, with the reduction of pro-inflammatory cytokine levels and tissue damage compared with the EPS-free groups suffering from C. albicans infection. Overall, these findings indicate that ObEPS has potent anti-inflammatory activity and may serve as a promising natural adjunct for mitigating infection-associated inflammatory damage. Full article

Background: Calciphylaxis (calcific uremic arteriolopathy), is a rare disease characterized by subcutaneous vascular thrombosis and necrotic skin lesions, which mainly affects patients with kidney disease. This condition often has a poor prognosis, unclear pathophysiology, and lacks standardized treatment. Case Description: We present a case of calciphylaxis in a 53-year-old female patient who reported gradually worsening unbearable pain in her lower limbs and thighs, persisting for approximately 18 months. After appropriate examinations and biopsy of non-healing wounds, histopathology confirmed the diagnosis of calciphylaxis. The wounds were treated with dermo-epidermal (DE) grafts. Followingly, the patient underwent treatment in a hyperbaric chamber, after which the wounds decreased in size. Conclusions: Early diagnosis and a comprehensive approach to therapy are necessary to improve the management of calcification, a rare disease, and complications such as non-healing wounds. Full article

Background: Static cold storage is the standard method of kidney preservation following donation after circulatory death (DCD). A previous study on rodent models demonstrated the efficacy of storing DCD kidneys at 22 °C in an extracellular-type solution (ETK). We evaluated the efficacy of storing warm-ischemic kidneys at 22 °C in MHC-inbred miniature swine. Methods: After 2 h warm ischemia, the kidneys were preserved in ETK for one hour at either 4 °C or 22 °C and then subjected to ex vivo normothermic machine perfusion (NMP) for 2 h (n = 3 in each group). The same warm-ischemic kidneys, preserved in ETK (n = 3 in each group) or intracellular-type solution (UW; n = 2 in each group) at either 4 °C or 22 °C, were transplanted into MHC-matched recipients. Results: Compared with kidneys preserved at 4 °C, those preserved at 22 °C showed significantly better physiological and metabolic indices during ex vivo NMP. Furthermore, renal function was significantly higher in transplanted kidneys, and graft biopsies on postoperative day 4 showed more localized necrosis in the renal tubules when kidneys were stored at 22 °C. In contrast, recipient animals with kidneys stored in UW solution did not survive for more than 7 days. Conclusions: Two-hour warm-ischemic kidneys from miniature swine showed improved preservation at 22 °C than at 4 °C when an extracellular-type solution was used. Full article